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Archives of Endocrinology and Metabolism Aug 2015Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase... (Review)
Review
Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.
Topics: Adipose Tissue, White; Humans; Lipase; Lipolysis
PubMed: 26331321
DOI: 10.1590/2359-3997000000067 -
The Journal of Cell Biology Jun 2003Successful adaptation to starvation in mammals depends heavily on the regulated mobilization of fatty acids from triacylglycerols stored in adipose tissue. Although it... (Review)
Review
Successful adaptation to starvation in mammals depends heavily on the regulated mobilization of fatty acids from triacylglycerols stored in adipose tissue. Although it has long been recognized that cyclic AMP represents the critical second messenger and hormone-sensitive lipase (HSL)**Abbreviations used in this paper: ADRP, adipocyte differentiation-related protein; HSL, hormone-sensitive lipase; PKA, protein kinase A; TAG, triacylglycerol. the rate-determining enzyme for lipolysis, simple activation of the enzyme has failed to account for the robust augmentation of fatty release in response to physiological agonists. In this issue, Sztalryd et al. (2003) provide convincing support to the notion that the subcellular compartmentalization of lipase also regulates lipolysis, and, more importantly, that proteins other than HSL are localized to the lipid droplet and are indispensable for its optimal hydrolysis.
Topics: Adipose Tissue; Animals; Cell Compartmentation; Humans; Lipid Metabolism; Lipolysis; Protein Transport; Sterol Esterase
PubMed: 12810703
DOI: 10.1083/jcb.200306008 -
The Journal of Experimental Biology Mar 2018The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy... (Review)
Review
The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy balance, lipolysis of triacylglycerols and re-esterification of free fatty acids are opposing processes operating in parallel at identical rates, thus allowing a more dynamic transition from anabolism to catabolism, and vice versa. In response to alterations in the state of energy balance, one of the two processes predominates, enabling the efficient mobilization or storage of energy in a negative or positive energy balance, respectively. The release of noradrenaline from the sympathetic nervous system activates lipolysis in a depot-specific manner by initiating the canonical adrenergic receptor-G-protein-adenylyl cyclase-cyclic adenosine monophosphate-protein kinase A pathway, targeting proteins of the lipolytic machinery associated with the interface of the lipid droplets. In brown and brite adipocytes, lipolysis stimulated by this signaling pathway is a prerequisite for the activation of non-shivering thermogenesis. Free fatty acids released by lipolysis are direct activators of uncoupling protein 1-mediated leak respiration. Thus, pro- and anti-lipolytic mediators are bona fide modulators of thermogenesis in brown and brite adipocytes. In this Review, we discuss adrenergic and non-adrenergic mechanisms controlling lipolysis and thermogenesis and provide a comprehensive overview of pro- and anti-lipolytic mediators.
Topics: Adipose Tissue; Adrenergic Agents; Adrenergic Antagonists; Lipolysis; Thermogenesis
PubMed: 29514884
DOI: 10.1242/jeb.165381 -
Nature Reviews. Endocrinology Sep 2022
Topics: Adipocytes; Bone Marrow; Bone and Bones; Humans; Lipolysis
PubMed: 35821109
DOI: 10.1038/s41574-022-00723-1 -
The New England Journal of Medicine Jul 2017
Topics: Atherosclerosis; Humans; Lipolysis; Triglycerides
PubMed: 28723326
DOI: 10.1056/NEJMe1706907 -
Current Protein & Peptide Science 2018Adipose triglyceride lipase (ATGL) is the key-enzyme for the release of fatty acids (FAs) from triacylglycerol (TG) stores during intracellular lipolysis producing FAs... (Review)
Review
Adipose triglyceride lipase (ATGL) is the key-enzyme for the release of fatty acids (FAs) from triacylglycerol (TG) stores during intracellular lipolysis producing FAs used for energy production. There is growing evidence that the products and intermediates from lipolytic breakdown during the FA mobilization process also have fundamental regulatory functions affecting cell signaling, gene expression, metabolism, cell growth, cell death, and lipotoxicity. Regulation of ATGL is therefore vital for maintaining a defined balance between lipid storage and mobilization. This review addresses the regulation of ATGL activity at the post-translational level with special emphasis on protein-mediated interaction at the site of hydrolytic action, namely to the lipid droplet.
Topics: Animals; Fatty Acids; Humans; Lipase; Lipid Metabolism; Lipids; Lipolysis; Molecular Structure; Protein Conformation; Signal Transduction; Triglycerides
PubMed: 28925902
DOI: 10.2174/1389203718666170918160110 -
Nature Reviews. Endocrinology Mar 2022
Topics: Fibroblast Growth Factor 1; Humans; Lipolysis; Signal Transduction
PubMed: 35046569
DOI: 10.1038/s41574-022-00634-1 -
Trends in Endocrinology and Metabolism:... Oct 2016The selective breakdown by autophagy of lipid droplet (LD)-stored lipids, termed lipophagy, is a lysosomal lipolytic pathway that complements the actions of cytosolic... (Review)
Review
The selective breakdown by autophagy of lipid droplet (LD)-stored lipids, termed lipophagy, is a lysosomal lipolytic pathway that complements the actions of cytosolic neutral lipases. The physiological importance of lipophagy has been demonstrated in multiple mammalian cell types, as well as in lower organisms, and this pathway has many functions in addition to supplying free fatty acids to maintain cellular energy stores. Recent studies have begun to delineate the molecular mechanisms of the selective recognition of LDs by the autophagic machinery, as well as the intricate crosstalk between the different forms of autophagy and neutral lipases. These studies have led to increased interest in the role of lipophagy in both human disease pathogenesis and therapy.
Topics: Animals; Autophagy; Humans; Lipid Droplets; Lipid Metabolism; Lipolysis; Perilipin-1
PubMed: 27365163
DOI: 10.1016/j.tem.2016.06.003 -
Advances in Experimental Medicine and... 1998Mechanisms regulating adipocyte lipolysis are reviewed in three stages. The first stage examines plasma membrane hormone receptors and G-proteins. The primary regulators... (Review)
Review
Mechanisms regulating adipocyte lipolysis are reviewed in three stages. The first stage examines plasma membrane hormone receptors and G-proteins. The primary regulators of adipose tissue lipolysis, the catecholamines, bind to the alpha 2, beta 1, beta 2, and beta 3 adrenergic receptors. The alpha 2 receptor couples with Gi-proteins to inhibit cyclic AMP formation and lipolysis, while the beta receptors couple with Gs-proteins to stimulate cyclic AMP formation and lipolysis. The beta 1 receptor may mediate low level catecholamine stimulation, while the beta 3 receptor, which is activated by higher levels of catecholamines, may deliver a more sustained signal. The second stage examines the regulation of cyclic AMP, the intracellular messenger that activates protein kinase A. Adenylyl cyclase synthesizes cyclic AMP from ATP and is regulated by the G-proteins. Phosphodiesterase 3B hydrolyzes cyclic AMP to AMP and is activated and phosphorylated by both insulin and the catecholamines norepinephrine and epinephrine. The third stage focuses on the rate-limiting enzyme of lipolysis, hormone-sensitive lipase (HSL). This 82 to 88 kDa protein is regulated by reversible phosphorylation. Protein kinase A activates and phosphorylates the enzyme at 2 sites, and 3 phosphatases have been implicated in HSL dephosphorylation. The translocation of HSL from the cytosol to the lipid droplet in response to lipolytic stimulation may be facilitated by a family of lipid-associated droplets called perilipins that are heavily phosphorylated by protein kinase A and dephosphorylated by insulin. As the mechanisms regulating adipocyte lipolysis continue to be uncovered, we look forward to the challenges of integrating these findings with research at the in situ and in vivo levels.
Topics: Adipocytes; Animals; Catecholamines; Humans; Lipolysis
PubMed: 9781323
DOI: 10.1007/978-1-4899-1928-1_15 -
Journal of Lipid Research Feb 1994Fatty acids are important oxidative fuel for liver, kidney, skeletal muscle, and myocardium. There has been much interest in the role of fatty acids in the pathogenesis... (Review)
Review
Fatty acids are important oxidative fuel for liver, kidney, skeletal muscle, and myocardium. There has been much interest in the role of fatty acids in the pathogenesis of non-insulin-dependent diabetes because they compete with glucose for oxygen and inhibit whole body glucose disposal via the 'Randle cycle,' Control of lipolysis in adipose tissue determines systemic fatty acid supply. A wide range of hormones and other substances have been recognized as regulators of lipolysis, but insulin and catecholamines appear to be the most important. The regulation of lipolysis, in most circumstances, provides a supply of lipid fuel exceeding the rate of lipid oxidation, requiring reesterification to triglyceride of surplus circulating free fatty acids. Thus, free fatty acid supply is usually not matched to the demand for lipid oxidation, and there is no known mechanism for accurately sensing such demand. This lax regulation may be disadvantageous in conditions such as aging, stress, obesity, and diabetes, where the antilipolytic effect of insulin is impaired and lipolysis is therefore increased. In these conditions, the surfeit of fatty acid may impair glucoregulation. In addition, the excess lipolysis may induce hypertriglyceridemia (via increased very low density lipoprotein production) and thus contribute to atherogenesis. Considerable additional research is needed in order to fully understand both normal lipolytic regulation and the abnormalities of lipolysis which accompany pathological conditions.
Topics: Adipose Tissue; Diabetes Mellitus; Fatty Acids; Humans; Lipolysis; Liver; Muscles; Obesity
PubMed: 8169522
DOI: No ID Found